CCl4 intoxication in rats results in a loss of hepatic mitochondrial structure and function, as indicated by low rates of coupled respiration in isolated mitochondria, swollen ultrastructural appearance, and a decline of cellular ATP levels. Administration of chloramphenicol (chloromycetin: CAP) simultaneously with CCl4 results in little disruption of mitochondrial function or morphology, maintenance of cellular ATP concentrations, and an increase of the LD50 of CCl4. An investigation of the protective mechanism was proposed that would use the optical isomer of CAP (L-CAP) and a sulfamyl derivative, Tevenel, to establish the mechanism of protection. Results of the first year's work have established that Tevenel (which, like CAP, inhibits mitochondrial protein synthesis) fails to protect, while L-CAP (inactive on mitochondrial protein synthesis) does protect. Having ruled out the involvement of mitochondrial protein synthesis in the CCl4 lesion, current work is directed toward establishing whether interaction of CAP with cellular membranes, including mitochondrial, or interference with CCl4-generated lipid peroxidation, is the mechanism of protection. Initial experiments do indicate that CAP is effective at preventing the disruption of microsomal protein synthesis that characterizes the early effects of CCl4 intoxication. Whether any interference with a CCl4-induced perturbation is relevant to the prevention of the mitochondrial lesion will be established by comparison with any effects elicited by L-CAP and Tevenel. Also, CAP protection will be compared with that offered by two known antagonists of CCl4 intoxication that are believed to act by interrupting CCl4-induced lipid peroxidation: SKF 525A and diphenyl-p- phenylenediamine.